ESC Study Group of Sports Cardiology Position Paper on

Position Paper
ESC Study Group of Sports Cardiology Position Paper on
adverse cardiovascular effects of doping in athletes
Asterios Deligiannisa, Hans Björnstadb, Francois Carrec, Hein Heidbücheld,
Evangelia Kouidia, Nicole M. Panhuyzen-Goedkoope, Fabio Pigozzif,
Wilhelm Schänzerg and Luc Vanheesh on behalf of the ESC Study Group
of Sports Cardiology
a
Laboratory of Sports Medicine, Aristotle University, Thessaloniki, Greece, bDepartment of Heart Disease,
Haukeland University Hospital, Bergen, Norway, cUnité Biologie et Médecine du Sport, Hôpital Pontchaillou,
Rennes, France, dUniversity Hospital Gasthuisberg, Leuven, Belgium, eDepartment of Cardiology, Radboud
University Hospital and Department of Sports Cardiology and Cardiac Rehabilitation, St Maartens Kliniek,
Nijmegen, The Netherlands, fSports Medicine Department, University Institute of Movement Sciences,
Roma, Italy, gInstitute of Biochemistry, German Sport University, Cologne, Germany and hDepartment of
Rehabilitation Sciences, Leuven, Belgium.
Received 28 December 2005 Accepted 27 April 2006
The use of doping substances and methods is extensive not only among elite athletes, but also among amateur and
recreational athletes. Many types of drugs are used by athletes to enhance performance, to reduce anxiety, to increase
muscle mass, to reduce weight or to mask the use of other drugs during testing. However, the abuse of doping substances
and methods has been associated with the occurrence of numerous health side-effects. The adverse effects depend on the
type of the consumed drug, as well as the amount and duration of intake and the sensitivity of the body, since there is a
large inter-individual variability in responses to a drug. Usually the doses used in sports are much higher than those used
for therapeutic purposes and the use of several drugs in combination is frequent, leading to higher risk of side-effects.
Among biomedical side-effects of doping, the cardiovascular ones are the most deleterious. Myocardial infarction,
hyperlipidemia, hypertension, thrombosis, arrythmogenesis, heart failure and sudden cardiac death have been noted
following drug abuse. This paper reviews the literature on the adverse cardiovascular effects after abuse of prohibited
substances and methods in athletes, aiming to inform physicians, trainers and athletes and to discourage individuals from
c 2006 The European Society of Cardiology
using drugs during sports. Eur J Cardiovasc Prev Rehabil 13:687–694 European Journal of Cardiovascular Prevention and Rehabilitation 2006, 13:687–694
Keywords: doping, cardiovascular side-effects, sports
Introduction
Doping is defined as ‘the presence of a Prohibited
Substance or its Metabolites or Markers in an Athlete’s
bodily Specimen and the Use or Attempted Use of a
Prohibited Substance or a Prohibited Method to increase
athletic performance’ [1]. In 1967, for the first time, the
International Olympic Committee (IOC) made up a list
of banned substances, which has been updated and
adapted to changes in the use of doping substances or
methods in sports ever since. Since 2004 the World AntiDoping Agency (WADA) has been coordinating the antidoping fight. In the WADA 2005 list of prohibited
substances and methods [2], the following categories of
substances are included:
Correspondence and requests for reprints to Dr Asterios Deligiannis MD,
Professor of Sports Medicine, 26 Agias Sofias Street, 546 22 Thessaloniki,
Greece.
Tel: + 30 2310 992181; fax: + 30 2310 992183;
e-mail: [email protected] med.auth.gr
(1) anabolic agents, hormones and related substances,
beta-2 agonists, agents with anti-estrogenic activity,
and diuretics and other masking agents are always
prohibited;
c 2006 The European Society of Cardiology
1741-8267 Copyright © European Society of Cardiology. Unauthorized reproduction of this article is prohibited.
688 European Journal of Cardiovascular Prevention and Rehabilitation 2006, Vol 13 No 5
(2) stimulants, narcotics, cannabinoids and glucocorticosteroids are prohibited in competition;
and
(3) alcohol and beta-blockers are prohibited in particular
sports.
In terms of prohibited methods the following categories
are included: enhancement of oxygen transfer; pharmacological, chemical and physical manipulation; and gene
doping.
All these are considered as doping and therefore are
forbidden, practically because of two main reasons:
performance enhancing and, thus, unfair competition,
and health risks. The health side-effects of doping
depend on the type of the consumed drug, as well as
the amount and duration of intake and the sensitivity of
the body. Additionally, athletes often use a combination of
several drugs at high doses, which are constantly
changing, leading to interactions and counteractions.
Among biomedical side-effects of doping, the cardiovascular ones are the most deleterious, with the potential
to lead to increased morbidity and mortality (Tables 1
and 2). It is important to stress, and easy to understand,
that only sparse data and isolated clinical cases
are actually available. Thus, despite the recent increase
in the number of publications, it is difficult to know the
real hazard and effects of doping drugs and methods upon
the cardiovascular system, particularly during acute
exercise.
Table 1
WADA doping list of drugs affecting cardiovascular system
Prohibited in competitive
sports
Prohibited
in certain
competitive
sports
Not prohibited
Stimulants
amphetamine
cocaine
ephedrine
fencamfamin
modafinil
nikethamide
Narcotics
morphine
pethidine
Beta-2 agonists
reproterol
isoprenaline
Masking drugs (diuretics)
amiloride
chlortalidone
etacrynic acid
furosemide
Anabolic steroids
testosterone
nandrolone
stanozolol
metandienone
Glucocorticosteroids
betamethasone
triamcinolone
Beta blockers
atenolol
bisoprolol
carvedilol
esmolol
labetolol
metoprolol
pindolol
propranolol
sotalol
Antihypertensive drugs
calcium blockers
ACE Inhibitors
AR Blockers
Local anesthetic
xylocaine
Analgesics
acetylsalicylic acid
Cholesterol-reducing drugs
fluvastatin
clofibrate
colestipol
ezetimibe
gemfibrozil
atorvastatin
acipimox
colestyramine
pravastatin
simvastatin
ACE, angiotensin-converting enzyme; AR, angiotensin II type 1 receptor.
Table 2
Cardiac side-effects of prohibited substances
AAS
hGH
EPO
Beta-2 agonists
Diuretics
Amphetamines
Cocaine
Ephedrine
Narcotics
Cannabinoids
Glucocorticosteroids
Alcohol
Hypertension
Arrhythmias
LVH
CAD
MI
HF
SCD
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+ Indicates an effect on a parameter; LVH, left ventricular hypertrophy; CAD,
coronary artery disease; MI, myocardial infarction; HF, heart failure; SCD, sudden
cardiac death; AAS, androgenic–anabolic steroids; hGH, human growth
hormone; EPO, erythropoietin.
Substances and methods prohibited at all times
Androgenic–anabolic steroids
The use of androgenic–anabolic steroids (AASs) is
common among all kind of athletes, amateur, elite and
recreational. Anabolic steroids have the potential to
increase lean muscle mass and strength under certain
conditions [3]. Tetrahydrogestrinone is a recently identified compound, being developed as a potent androgen
[4]. Several reports associate AAS abuse with serious
cardiovascular disorders, such as ischemic heart disease,
arterial hypertension, cardiomyopathy, heart failure, QT
dispersion, arrhythmias, ventricular thrombosis, etc.
[5,6]. Myocardial infarction and sudden cardiac death
are reported as the most dramatic manifestations in
athletes who had taken massive amounts of AASs [5,7–9].
Melchert and Welder [10] demonstrated four hypothetical models of anabolic-induced adverse cardiovascular
effects:
(1) an ‘atherogenic’ model involving the effects of AASs
on lipoprotein concentrations;
(2) a ‘thrombogenic’ model involving the effects of AASs
on clotting factors and platelets;
(3) a ‘vasospasm’ model involving the effects of AASs on
the vascular nitric oxide system;
(4) a ‘direct myocardial injury’ model involving the
effects of AASs on myocardial cells.
Lipoprotein profile and atherogenesis AAS administration is
found to cause a marked reduction of high-density
lipoprotein (HDL) cholesterol that ranges from 39 to
70% [11]. The effects are dose dependent and vary with
types of substances used. The most pronounced decrease
is shown within a few days after starting the intake and
after about 8 weeks no further alteration is observed
[12,13]. Particularly, HDL2-cholesterol seems to be most
affected [12,13]. It is found that the orally taken 17aalkylated substances are most potent in this respect [12].
Copyright © European Society of Cardiology. Unauthorized reproduction of this article is prohibited.
Adverse cardiovascular effects of doping in athletes Deligiannis et al. 689
The stimulation of hepatic triglyceride lipase that
regulates serum lipids is responsible for this reduction
[14]. In parallel, there is an increase of low-density
lipoprotein (LDL) cholesterol, especially caused by oral
administration [12]. Additionally, AASs induce a decline
in apolipoprotein B-1 and increases of apolipoprotein A
[12,13]. On the other hand, most studies in athletes
found no changes of either cholesterol or triglyceride
levels due to AAS administration [12,13]. There is
evidence that several AASs in high doses beneficially
alter lipoprotein (a) levels [15]. However, there is a
complete recovery of serum lipid and lipoproteins after
AAS withdrawal within a few months, which depends on
the duration of intake [13]. Androgens may also be proatherogenic, promoting cell adhesion [16]. Additionally,
they are found to promote monocyte adhesion to
endothelial cells and macrophage lipid loading [17,18].
Thrombogenesis AASs have been demonstrated to decrease
fibrinolytic activity and synthesis of prostacyclin and to
increase platelet aggregation and endothelium release of
proteins C and S [19–21]. Additionally, AAS abuse is found
to affect the hemostatic system, causing its accelerated
activation, as evidenced by increased generation of both
thrombin and plasmin [21,22]. These changes could
reflect a thrombotic diathesis that may contribute to
vascular occlusion. These adverse effects are exacerbated
in cases of dehydration and catecholaminergic stress which
are often associated with physical exercise.
Coronary vasoconstriction Testosterone has been found to
inhibit extraneuronal uptake of neuroamines and increase
the vascular response to norepinephrine. Sader et al. [23]
found that the use of AASs is associated with impaired
vascular reactivity, but not with arterial thickening or
endothelial dysfunction. AASs are associated with impaired
arterial reactivity and enhanced endothelium-dependent
dilatation in adult men [24,25]. However, the use of AASs
was not associated with significant arterial thickening and
endothelial dysfunction in healthy young men [23].
Direct myocardial injury AAS intake leads to myocyte
hypertrophy [26,27] with changes in the contractile
apparatus, with disintegration and Z-band distortions or
dissolution in the sarcomere, to disturbances in the
mitochondria (like swelling damage), change of myofibril/
mitochondria ratio and to intracellular lipid accumulation
[28]. Moreover, cellular swelling and increased intercellular collagen deposition have been reported [29].
Luke et al. [30] found extensive myocardial fibrosis, foci
of necrosis and myocytes with contraction band necrosis
in a weight-lifter using anabolic steroids. Also, lack of
blood supply in a hypertrophic myocardium may contribute to myocardial fibrosis [31]. Additionally, there is
evidence that AASs induce apoptotic cell death in adult
ventricular myocytes, affecting cardiac contractility [32].
The effects of AASs on global left ventricular (LV)
structure and function are still unequivocal. A majority of
echocardiographic studies have shown larger posterior
wall and interventricular septal thickness, as well as an
increased LV mass and mass index with the use of AASs
[33–35]. On the contrary, some studies have not observed
any differences in the echocardiograms between AAS
users and non-users in strength athletes [36,37]. Additionally, AAS intake was not found to affect LV systolic
and possibly diastolic function [34–36]. However, there is
evidence that the use of AASs leads to a decrease in the
contribution of LV passive filling to LV filling associated
with a decrease in LV relaxation properties [38,39].
AASs may influence LV structure through direct adverse
myocardial effects (as mentioned above) reinforced by
mineralocorticoid-like effects causing hypertension.
Thus, unlike the physiological cardiac hypertrophy
observed after physical training, cardiac hypertrophy
induced by AAS is pathological, with an increased fibrosis
and an inadequate myofibril/arterial vessel ratio. When
cardiac hypertrophy is observed it persists after the
cessation of AAS abuse [40].
Cardiac arrhythmias AASs are pro-arrhythmic through the
myocardial structural changes they may induce, as
described above. Moreover, they have electrophysiological
effects. They cause a profound and prolonged depression
of the stimulation threshold of the heart [41]. Additionally, they influence electrolyte concentrations, increasing
levels of potassium, sodium, calcium and phosphate,
which can ultimately result in atrial and ventricular
fibrillation [42,43]. Nieminen et al. [21] reported the
increased automaticity as the possible electrophysiological mechanism of ventricular fibrillation, which was
observed in an athlete using anabolics. AASs also affect
the cardiac sympathetic nervous system, causing transient depletion and degeneration of sympathetic axon
terminals [44]. Anabolic agents have been shown to
increase the pressor response to catecholamines in
animals [45]. All these alterations may lead to an
increased vulnerability to serious dysrhythmias.
Blood pressure An elevation of either systolic and or
diastolic blood pressure (BP) has been observed as a
result of AAS abuse in many studies [46,47]. Androgens
seem to have a more intense effect on BP than anabolics,
mainly due to sodium and water retention [46]. On the
other hand, there are studies that could not detect any
significant alteration of BP in athletes who used AASs
[35,48].
Peptide hormones, mimetics and analogues
The most commonly used substances from this class are
human growth hormone (hGH) and insulin-like growth
factor 1 (IGF-1), as well as erythropoietin (EPO).
Copyright © European Society of Cardiology. Unauthorized reproduction of this article is prohibited.
690 European Journal of Cardiovascular Prevention and Rehabilitation 2006, Vol 13 No 5
Human growth hormone (hGH) and insulin-like growth
factor 1 Chronic hGH excess leads to cardiomyopathy,
characterized by myocardial hypertrophy with interstitial
fibrosis, lympho-mononuclear infiltration and areas of
monocyte necrosis. Additionally, hGH excess increases
the incidence of arrhythmias and thus cardiovascular
mortality [49].
Erythropoietin There is a dose-dependent increase in
hematological parameters after administration of recombinant human erythropoietin (rHuEPO) [50]. Its effects
last several days after its last intake, when the
erythropoietin concentrations are in the range of normal
values [51]. The misuse of rHuEPO causes increased
viscosity of the blood which, in combination with the
elevated hematocrit, leads to increased risk of thrombosis
and embolisms [52]. Additionally, increased afterload,
elevated blood viscosity and the loss of hypoxia-induced
vasodilation lead to arterial hypertension and perhaps to
cardiac dysfunction [53]. A fatal reduction of heart rate
during the night has also been reported [54].
Beta-2 agonists
Beta-2 agonists, such as clenbuterol and salbutamol,
when administered orally, appear to improve muscular
strength due to their potential role in increasing muscle
mass. Clenbuterol is also popular for its reduction of
subcutaneous fat [55]. It is well known that formoterol,
salbutamol, salmeterol and terbutaline are widely used in
treating asthma. Thus, they are allowed to be administered by inhalation, if the athlete has applied in advance
for a therapeutic use exception (TUE). Use of beta-2
agonists has been found to increase the risk for adverse
cardiovascular events. They may precipitate ischemia,
congestive heart failure, arrhythmias and sudden death
[56]. They activate cardiac and peripheral beta-2
adrenoceptors, inducing positive chronotropic and inotropic effects and vasodilation with coronary blood flow
redistribution [56,57]. Additionally, initiation of treatment reduces potassium concentrations and causes other
metabolic and electrical changes, including prolonged QT
interval [57]. Chodorowski and Sein-Anand [58] described a case of acute, unintentional intoxication with
clenbuterol in a bodybuilder, who appeared with tachycardia, headache, dizziness, tremor, sweats, muscle
weakness and agitation.
Diuretics and other masking agents
Diuretics may be taken mainly to mask drug contents in
the urine [3]. Diuretics may cause imbalance of
electrolytes leading to arrhythmias. Especially, inhibition
of hydroxysteroid dehydrogenase is found to cause an
increase in cholesterol and triglyceride levels [59]. In
athletes with silent genetic mutations of sodium and
potassium channels, electrolytic imbalance may lead to
subsequent QT prolongation and arrhythmias.
Substances and methods prohibited only in competition
Stimulants
Stimulants, like amphetamines and cocaine, act on the
central nervous system through dopamine, norepinephrine and serotonin secretion.
Amphetamines Amphetamines may increase time to exhaustion by masking the physiological response to fatigue
[3]. Amphetamine intoxication or long-term exposure can
result in stroke, hypertension, tachycardia or bradycardia,
cardiac rhythm disturbances, coronary events, coma and
death [3,60,61]. Smoking of crystal methamphetamine, as
well as chronic oral abuse of dextroamphetamine, are
reported to have caused cardiomyopathy [62,63]. In
another case, smoking of crystal methamphetamine has
produced diffuse vasospasm that resulted in acute
myocardial infarction, cardiogenic shock and death [63].
Cocaine Cocaine is an alkaloid extracted from the
erythroxylon coca. Cocaine and other sympathomimetic
drugs seem to have little or no effect on athletic
performance [3]. Myocardial ischemia and infarction in
individuals with normal or atherosclerotic coronary arteries
have previously been described as an important causative
factor of morbidity and mortality [64,65]. Cocaine has a
local anesthetic property on the heart, due to its ability to
block sodium and potassium channels, as well as a
potent sympathomimetic and a vagolytic effect [66,67].
Moreover, it increases adenyl cyclase activity [65]. Interestingly, development of myocardial infarction is independent of cocaine dose [65]. The possible mechanisms by
which cocaine causes myocardial ischemia and coronary
artery thrombosis include an increase in myocardial oxygen
demand (increasing heart rate and blood pressure), a
decrease in oxygen supply as a result of coronary vasospasm
and, also, an ingressive thrombogenesis [65–68]. Ventricular
arrhythmias, QT- and PR-interval prolongation, and A-V
conduction disorders are a precursor to sudden death in
cocaine users [69]. It is likely that cocaine induces
ventricular arrhythmias with or without underlying myocardial pathology [65,66]. Rapid adrenergic stress, local
anesthetic properties and a direct toxic effect of cocaine on
the myocardium are related with the arrhythmic potential
of the drug [65,66]. Pulmonary edema mediated by
increased endothelial permeability of the capillaries is seen
commonly in crack abuse [68]. Other cardiovascular
adverse reactions include the appearance of myocarditis
and dilated cardiomyopathy, infective endocarditis, ruptured aortic aneurysm, vascular thrombosis, hypertension
and cerebrovascular accidents [64,65]. Death from cocaine
can occur within some minutes, suggesting direct cardiac
toxicity, fatal arrhythmia and depression of medullary
respiratory centers [67].
Ephedrine alkaloids Ephedrine is effective orally and
appears to have longer-acting potency than catecholamines.
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Adverse cardiovascular effects of doping in athletes Deligiannis et al.
691
Ephedrine-containing preparations, such as ma-huang,
‘herbal Ecstasy’ and others, in small dosages stimulate
the heart, increasing the rate and force of contraction [70].
Moreover, ephedrine raises the blood pressure by constriction of blood vessels [70]. Several studies have shown that
ephedra abuse may lead to acute constriction and
thrombosis of the coronary and other arteries [70,71].
Moreover, the adrenergic effects of ephedrine may lead to
the development of cardiac arrhythmias [70,71]. Therefore,
cardiovascular complications, such as acute myocardial
infarction, severe hypertension, myocarditis, stroke, arrhythmias and sudden cardiac death, have become a
recognized problem due to ephedrine use in athletes
[70–73].
These include suppression of the hypothalamic–pituitary
axis, osteoporosis, reduced bone growth in the young,
opportunistic infections, behavioral alterations, and disorders of lipid metabolism, such as elevations of total
plasma cholesterol, triglycerides and LDL cholesterol
[78]. Dyslipidemia is caused by increased plasma insulin
levels, impaired lipid catabolism and increased lipid
production by the liver [79]. Hypertension is a major
adverse effect of high doses and prolonged intake of
glucocorticoids [79]. The possible mechanism is increased systemic vascular resistance, increased extracellular volume and increased cardiac contractility [79].
Narcotics
Alcohol is the oldest social beverage and principal drug of
abuse in the USA and other countries [80]. Alcohol does
not possess an ergogenic effect. However, it may be used
to reduce anxiety or tremor prior to competition [3].
Moderate drinkers consume one or two drinks per day,
while heavy drinkers consume more than five drinks per
day, each of which contains 13 g of alcohol [81]. Initially,
alcohol consumption may lead to increased heart and
respiratory rate, superficial vasodilation and a rise in blood
pressure [66,82]. Adverse consequences of alcohol use are
hypertension, stroke, coronary events, cardiac arrhythmias
and dilated cardiomyopathy [65,66,83]. The precise
mechanism by which alcohol produces hypertension and
stroke is unknown. Moreover, the effects of alcohol
consumption on coronary artery disease are controversial
[65]. Adrenergic activity in heavy drinkers causes
hypertension, tachycardia and coronary spasm, leading
to increased risk for ischemic heart disease and sudden
cardiac death [84]. On the other hand, there is a lower
incidence of coronary atherosclerosis in moderate drinkers [85]. The cardio-protective effect of moderate
alcohol consumption is partly due to its favorable effect
on HDL level and fibrinolytic activity [86]. Additionally,
alcoholics may have low LDL levels. However, moderate
alcohol consumption is found to increase apolipoproteins
(apo) A-I, A-II and high-density lipoprotein subfraction
(HDL3) without affecting other lipoproteins [86,87].
Some preparations (for example, morphine, heroin,
codeine) are derived directly from opium, while others
are semi-synthetic or entirely synthetic. Narcotic analgesics are not necessarily ergogenic but their use can be
harmful in cases where they allow the participation of an
athlete with a severe injury [3]. Opium is a strong
respiratory depressant, but affects heart rate and blood
pressure to only a minor degree [74,75]. The main toxic
effects are respiratory depression, coma and death [75].
Cannabinoids
The most commonly used preparations of cannabis are
marijuana and hashish. Maximal blood concentrations of
the main active ingredient, tetrahydrocannabinol (THC),
are attained 3–8 min after a cigarette smoke and the peak
effect in 2–4 h, lasting for 4–6 h [76]. Concentrations of
the main metabolite, carboxy-THC > 15 mg/l in urine
samples are considered as doping. THC acts primarily via
b-adrenergic stimulation and possibly also by parasympathetic blockade. It increases heart rate and decreases
cardiac stroke volume. The increased sympathetic
activity in combination with interference with the
integrity of the peripheral vascular reflex responses and
arterial vasospasm effects leads to the appearance of
tachycardia, and, also, vascular reflex failure [77]. These
pathophysiologic mechanisms are responsible for increased myocardial oxygen demand and decreased oxygen
delivery and, thus, can result in acute ischemia and/or
arrhythmias [65,77]. Therefore, myocardial infarction,
stroke and sudden cardiac death may occur from using
cannabis preparations [77].
Glucocorticosteroids
Glucocorticosteroids may be used by topical, inhalation or
intra-articular routes of administration. For the use of
non-systemic preparations a therapeutic use exception
(TUE) has to be applied. All kinds of systematic
application (oral, i.m. and i.v. injections) are not allowed.
The long-term use of glucocorticosteroids is associated
with serious and sometimes irreversible side-effects.
Substances prohibited in particular sports
Alcohol
Beta-blockers
The use of beta-blockers in endurance sports causes a
decrease of physical capacity due to the negative effect
on energetic metabolism [88]. The reduction in endurance capacity is found to be related mainly to lipid
metabolism and possibly to K + efflux, but not to hemodynamics [89,90].
However, in the case of high psychological strain, betablockers lead to a decrease of stress caused by competition [91]. Their use leads to significant decreases of heart
rate and blood pressure [91]. As a possible reason for
increased physical capacity after sympathicolysis, changes
Copyright © European Society of Cardiology. Unauthorized reproduction of this article is prohibited.
692
European Journal of Cardiovascular Prevention and Rehabilitation 2006, Vol 13 No 5
of cardiovascular parameters as well as central influences
are conceivable [91].
Prohibited methods
Blood doping, artificial oxygen carriers or plasma
expanders
Blood doping increases red blood cell mass to deliver
more oxygen to muscle, leading to an increase of physical
capacity. Erythrocytosis results in tachycardia and an
increased afterload, which may lead to hypertension,
myocardial infarction and cardiac insufficiency [53].
Additionally, there is an increased risk of blood clots.
Substance abuse in sports
There are substances, such as nicotine, antidepressants,
caffeine, etc., which are often used by athletes as a part of
their lifestyle and abused in an attempt to improve
athletic performance, although they are not considered
prohibited. Many of the abused agents may, however,
have adverse effects on the cardiovascular system.
Caffeine
Caffeine may improve the utilization of fatty acids as a
fuel source, thereby sparing muscle glycogen [3].
Caffeine enhances the cardiovascular and central nervous
system effects of ephedrine. It acts competitively,
antagonizing the receptors for adenosine and augments
the release of catecholamines [3,65,92]. Large doses of
caffeine increase cardiac activity and cause peripheral
vasodilation [83]. Rarely, adverse reactions to caffeine are
severe; for example, hypertension, cholesterol abnormalities, arrhythmias, coma and death [65,92]. More often,
caffeine abuse leads to palpitations and chest pain
[65,66,85]. Caffeinism is a syndrome resulting from the
excessive ingestion of caffeine, characterized by respiratory alkalosis with cardiovascular and central nervous
system disorders [93].
Smokeless tobacco
Tobacco products may produce psychomotor effects or
control appetite, which may be beneficial to some
athletes [3]. The use of smokeless tobacco in sports is
increasing, with adolescents accounting for the majority
of users [94]. It is well known that nicotine abuse may
lead to elevation of total cholesterol and depression of
HDL [95]. Moreover, it causes intense vasoconstriction
of diseased and normal coronary artery segments [65,66].
In addition to atherogenic and vasospasm effects,
nicotine has thrombogenic actions resulting in increased
coagulability [65]. Another adverse effect of smokeless
tobacco is adrenergic stimulation, which may cause
cardiac arrhythmias. Also, a reduced threshold for
ventricular fibrillation following tobacco consumption
has been reported [65]. Thus, it is recommended that
tobacco is avoided for 2 h before and after a sports session
or practice.
Nutritional supplements
Nutritional supplementation, such as proteins, creatine,
vitamins or carnitine, is commonly used by both athletes
and people engaged in recreational sports. No strong
evidence linking nutritional supplementation to cardiac
side-effects has been found. In fact, most reports on sideeffects remain anecdotal because the case studies do not
represent well-controlled trials. Additionally, data with
regard to long-term safety of nutritional supplementation
are lacking. Nutritional or herbal supplements may have
harmful effects on arrhythmias [96]. The use of cesium
chloride as a dietary supplement is potentially hazardous
as it may induce fatal ventricular arrhythmias [97].
Moreover, chronic excess of calcium intake may also
contribute to dysrhythmias.
In practice, several drugs are frequently used in
combination, which may lead to interactions and a higher
risk of cardiovascular side-effects than described for any
of the substances above. For example, the intake of
anabolic steroids, amphetamines, frumil and potassium
supplements caused myocardial infarction, hyperkalemia
and ventricular tachycardia in a young bodybuilder [98].
Moreover, herbal preparations containing both ephedrine
and caffeine, as ‘herbal Ecstasy’, or other compositions
may often lead to adverse reactions, ranging from minor
to major, such as palpitations, hypertensive crises and
severe ventricular arrhythmias [71,99]. When examining
an athlete with unexpected cardiac symptoms, physicians
should suspect the abuse of substances. Testing to detect
abused substances by systematic sampling of urine or
blood is important to prevent adverse events and to
ensure fair competition. The target is to obtain a highly
accurate and sensitive assessment of the used substances
in urine, long enough after the intake.
Acknowledgements
The authors would like to thank the following members
of the Study Group of Sports Cardiology who contributed
to this position paper: Antonio Pellicia, Alessandro Biffi,
Domenico Corrado, Andreas Hoffmann, Asle Hirth,
Deodato Assanelli, E Arbustini, Dorian Dugmore, Hellen
Hoffmann, Pietro Delise, Robert Fagard, Silvia Priori,
William McKenna, Aris Anastasakis, Uwe Dorwarth, Tony
Reybrouck, Jeff Senden, Michael Glickson, Klaus Peter
Mellwig, Jan Oudhof, Erik Solberg, Frank van Buuren,
Carina Blomstrom-Lundqvist, Birna Bjarnason-Wehrens,
Anneli Ulfward, Dany Maradet, Maria Penco and
Mohamed Thami.
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